芍药苷通过调控肠道菌群改善α-异硫氰酸酯诱导胆汁淤积大鼠的作用机制研究  

Mechanism of paeoniflorin in improvingα-isothiocyanate induced cholestasis by regulating intestinal flora in rats

作　　者：吴和霏 章方玲 邓昕雨 李煜兵 陈沅 胡启超 马骁[1] 赵艳玲 WU He-fei;ZHANG Fang-ling;DENG Xin-yu;LI Yu-bing;CHEN Yuan;HU Qi-chao;MA Xiao;ZHAO Yan-ling(State Key Laboratory of Southwest Characteristic Chinese Medicine Resources,College of Pharmacy,Chengdu University of Chinese Medicine,State Key Laboratory of Southwest Characteristic Chinese Medicine Resources,Chengdu 611137,China;Department of Pharmacy,Chinese PLA General Hospital,Beijing 100037,China)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,四川成都611137 [2]解放军总医院医疗保障中心药剂科,北京100037

出　　处：《中草药》2022年第22期7091-7101,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82274187);四川省科技厅应用基础项目(2019YJ0492)。

摘　　要：目的确证芍药苷对α-异硫氰酸酯(α-isothiocyanate,ANIT)诱导胆汁淤积大鼠的药效作用,通过16S rRNA技术探究芍药苷对肠道菌群的调节作用机制。方法SD大鼠随机分为对照组、模型组及芍药苷高、中、低剂量(200、100、50mg/kg)组和熊去氧胆酸(60 mg/kg)组,每组10只。给予药物干预7 d,第4天ig ANIT(60 mg/kg)诱导胆汁淤积模型。测定胆汁体积流量;检测血清中血清中天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,γ-GT)活性及总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、总胆汁酸(total bile acid,TBA)水平;采用苏木素-伊红(HE)染色观察肝脏组织病理变化;收集大鼠肠内容物进行肠道菌群测序,探索芍药苷对肠道菌群的影响。结果与模型组比较,芍药苷有效改善胆汁体积流量(P<0.05),显著下调大鼠血清中肝功能指标AST、ALT、γ-GT活性及胆汁淤积指标TBIL、DBIL、TBA水平(P<0.01),改善肝细胞损伤。肠道菌群测序结果可知,芍药苷显著上调厚壁菌门与拟杆菌门比值及异杆菌属Allobaculum、布劳特氏菌属Blautia丰度(P<0.05),降低颤螺菌属Oscillospira、瘤胃球菌属Ruminococcus丰度(P<0.05、0.01)。结论芍药苷可能通过改善ANIT诱导的胆汁淤积大鼠肠道菌群失调,从而发挥对胆汁淤积肝损伤的改善作用。Objective To verify the pharmacodynamic effect of paeoniflorin onα-isothiocyanate(ANIT)-induced cholestasis in rats,and explore the regulatory mechanism of paeoniflorin on intestinal flora by 16S rRNA technology.Methods SD rats were randomly divided into control group,model group,paeoniflorin high-,medium-and low-dose(200,100,50 mg/kg)groups and ursodeoxycholic acid(60 mg/kg)group,with 10 rats in each group.After 7 d of drug intervention,model of cholestasis was induced by ig ANIT(60mg/kg)on 4th day.Bile volume flow was measured;Activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyl transpeptidase(γ-GT)and levels of total bilirubin(TBIL),direct bilirubin(DBIL),total bile acid(TBA)in serum were detected;Hematoxylin eosin(HE)staining was used to observe the pathological changes of liver tissue;Intestinal contents of rats was collected for intestinal flora sequencing to explore the effect of paeoniflorin on intestinal flora.Results Compared with model group,paeoniflorin effectively improved bile volume flow(P<0.05),significantly down-regulated liver function index AST,ALT,γ-GT activities and cholestatic index TBIL,DBIL and TBA levels(P<0.01),improved the damage of liver cells.The sequencing results of intestinal flora showed that paeoniflorin significantly increased the ratio of Firmicutes/Bacteroides and abundance of Allobaculum and Blautia(P<0.05),and decreased the abundance of Oscillospira and Ruminococcus(P<0.05,0.01).Conclusion Paeoniflorin may improve the liver injury of cholestasis by improving the imbalance of intestinal flora in ANIT-induced cholestasis rats.

关 键 词：芍药苷 α-异硫氰酸酯 胆汁淤积 药效 16S rRNA 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]